Retention of technetium-99m in infectious foci in rats after release from technetium-99m labelled human non-specific polyclonal immunoglobulin G: A dual-label study with hydrazinonicotinamido and iminothiolano immunoglobulin

Abstract

In an effort to contribute to the understanding of the mechanism of uptake of technetium-99m labelled non-specific polyclonal human immunoglobulin G (hIgG) in inflammatory lesions we compared the tissue distribution of double-labelled^99mTc-hydrazinonicotinamido (HYNIC) hIgG-¹⁴C and^99mTc-iminothiolano hIgG-¹⁴C in groups of five Wistar rats with aStaphylococcus aureus infection of the left calf muscle between 2 h p.i. and 24 h p.i. The stability of the two double-labelled hIgG preparations was evaluated in vitro and in plasma in vivo by high-performance liquid chromatography (HPLC) analysis. At 24 h after injection of^99mTc-HYNIC-hIgG-¹⁴C the abscess uptake of^99mTc (1.5% ID/g±0.2% ID/g) was significantly higher (P<0.01) than the¹⁴C uptake (1.0% ID/g±0.1% ID/g). After injection of^99mTc-iminothiolano hIgG-¹⁴C no significant difference (P=0.08) was found between the abscess uptake of the two radionuclides at 24 h p.i. (^99mTc: 0.8% ID/g±0.1% ID/g;¹⁴C: 0.90% ID/g±0.09% ID/g). HPLC analysis of plasma samples revealed release of^99mTc from both double-labelled immunoglobulin preparations. This phenomenon was more pronounced for iminothiolano hIgG than for HYNIC hIgG (43% vs 18%). In most tissues other than abscesses significant differences were also found between the^99mTc and the corresponding¹⁴C uptake. Our results demonstrate that the chemical form in which^99mTc is bound to hIgG severely influences its release from hIgG and its retention in infections.